Rearrangement — [1,2]-anionic shift
[1,2]-Wittig rearrangement
How the [1,2]-Wittig rearrangement works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: n-BuLi (or other strong base); then H₃O⁺. Conditions: THF or Et₂O, –78 to 0 °C. Bonds formed: C–C; alkoxide (→ C–OH); bonds broken: α C–H; C–O (migrating group). Stereochemistry: Migrating-group stereochemistry retained (partial inversion in radical pair). Rate and selectivity: Migratory aptitude: tertiary > secondary > primary > methyl (radical stability).
At a glance
Step 1: Deprotonation α to oxygen
Strong base deprotonates a carbon alpha to an ether oxygen, generating a carbanion directly adjacent to that oxygen.
Step 2: [1,2]-shift from O to C
One of the ether's other carbon substituents migrates from oxygen directly onto the carbanion carbon in a concerted (or radical-pair) 1,2-shift — an anionic relative of the same migration logic seen in pinacol and Beckmann rearrangements.
Step 3: Protonation on workup
The result is an alkoxide, protonated on workup to give an alcohol — a way to convert an ether into an alcohol with a new C–C bond formed at the position that was originally attached to oxygen.
Abbreviations and terms
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- Et2O
- Diethyl ether. Low-boiling ether solvent, classic for Grignard reagents.
- n-BuLi
- n-Butyllithium. Very strong base/nucleophile (pKa of butane ≈ 50); deprotonates alkynes and does lithium–halogen exchange.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
How it compares with related reactions
| [1,2]-Wittig rearrangement | Meisenheimer rearrangement | Pinacol rearrangement | |
|---|---|---|---|
| Reagents | n-BuLi (or other strong base); then H₃O⁺ | Allylic tertiary amine N-oxide | Cat. H₂SO₄ or other strong acid |
| Conditions | THF or Et₂O, –78 to 0 °C | Heat, 25–100 °C (neutral) | Heat, aqueous or neat acid |
| Stereochemistry | Migrating-group stereochemistry retained (partial inversion in radical pair) | Suprafacial [2,3]; chirality transfer from N-oxide to carbon | Migratory aptitude: aryl, H > tertiary alkyl > methyl |
| Rate / selectivity | Migratory aptitude: tertiary > secondary > primary > methyl (radical stability) | Concerted, 5-membered envelope TS; unimolecular | Ionisation to the cation is rate-determining |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the [1,2]-Wittig rearrangement?
n-BuLi (or other strong base); then H₃O⁺. Conditions: THF or Et₂O, –78 to 0 °C.
Which bonds are formed and which are broken?
Formed: C–C; alkoxide (→ C–OH). Broken: α C–H; C–O (migrating group).
What is the stereochemical outcome?
Migrating-group stereochemistry retained (partial inversion in radical pair)
What controls the rate or the selectivity?
Migratory aptitude: tertiary > secondary > primary > methyl (radical stability)
Study guides that help with this reaction
- Pericyclic reactions explained: cycloadditions, electrocyclisations and sigmatropic shifts
- Stereochemistry in mechanisms: inversion, retention, syn and anti